Role of oestrogen receptors α and β in immune organ development and in oestrogen-mediated effects on thymus

Oestrogens affect the development and regulation of the immune system. To determine the role of oestrogen receptors α (ER-α and β (ER-β) on the development of the immune system, male ER-α (ERKO) and ER-β (BERKO) mice, as well as αβ-double knockout (DERKO) mice, were studied. Deletion of ER-α led to hypoplasia of both thymus and spleen. Interestingly, a higher frequency of immature double CD4⁺ CD8⁺ thymocytes was found in ER-α^- mice compared with ER-α⁺ mice. Female oophorectomized BERKO mice given oestradiol (E2) displayed a similar degree of thymic atrophy compared with the wild-type strain but showed only limited involution of thymus cortex and no alteration of thymic CD4/CD8 phenotype expression. Our data demonstrate that expression of ER-α, but not ER-β, is mandatory in males for development of full-size thymus and spleen, whereas expression of ER-β is required for E2-mediated thymic cortex atrophy and thymocyte phenotype shift in females. A potential background for the above findings may be down-regulated activity in the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis in males lacking ER-α and suppressed sensitivity of females lacking ER-β to E2-mediated suppression of IGF-1.